Previous studies on the relationships of diet to vascular disease have focused upon saturated fatty acids and polyunsaturated fatty acids (omega-6). We wish to study the effects of a unique class to fatty acids - omega-3 derived from fish oils. Preliminary data suggests that the feeding of fish oils results in reduction of plasma cholesterol and triglyceride levels and a second effect, prolongation of bleeding time. We wish to pursue these observations in a larger and more varied group of subjects under the rigorous conditions of an established Clinical Research Center. A fish oil (salmon) will be fed to human volunteers and certain observations made: 1) the uptake and composition of omega-3 fatty acids in plasma lipids, lipoproteins and tissues, specifically platelets and erythrocytes; 2) the time course and magnitude of the plasma cholesterol and triglyceride lowering effects; and 3) whether the incorporation of these fatty acids into platelets will produce alterations in platelets or platelet-endothelial cell interaction. We will study normal individuals, those with type IIa and IIb hyperlipoproteinemia, and patients with thrombotic vascular disease associated with documented "hyper-reactive" platelets (e.g. diabetes mellitus, atherosclerosis). Each subject will be studied during a "normal" American diet (high in saturated fatty acids), during a diet high in vegetable polyunsaturated fatty acids, and during a period in which the dietary fatty acids are derived almost entirely from fish oil. Using this model, we will investigate the following: 1) the relationship of plasma and platelet omega-3 fatty acids, 2) mechanisms of plasma cholesterol and triglyceride lowering effects of omega-3 fatty acids by assays of lipoprotein lipase activity, lipoproteins, apolipoproteins and the the sterol balance, and 3) alterations in platelet function by measurement of platelet adhesion, aggregation, release, prostaglandin synthesis and tests of platelet hyper-reactivity. The results of these studies may lead to beneficial dietary modification and advance our understanding of atherosclerotic vascular disease.